Does Invirase (saquinavir) cause side effects?

Invirase (saquinavir) is a type of antiviral medication called a protease inhibitor used to treat infections with the human immunodeficiency virus (HIV).

During infection with HIV, the HIV virus multiplies within the body’s cells. Viruses are released from the cells and spread throughout the body where they infect other cells.

During the production of the viruses, new proteins are made. Some of the proteins are structural proteins, that, is, proteins that form the body of the virus. Other proteins are enzymes which manufacture DNA and other components for the new viruses.

Protease is the enzyme that forms the new structural proteins and enzymes. Invirase blocks the activity of protease and results in the formation of defective viruses that are unable to infect the body's cells. As a result, the number of viruses in the body (the viral load) decreases. Invirase does not prevent the transmission of HIV among individuals, and it does not cure HIV or AIDS

Common side effects of Invirase include

Serious side effects of Invirase include

Drug interactions of Invirase include triazolam, midazolam, sildenafil, and ergotamine derivatives because Invirase increases the concentration of these drugs in the body and this could cause serious side effects.

Invirase also may inhibit the breakdown of the cholesterol-lowering drugs lovastatin, simvastatin, atorvastatin, and cerivastatin, which may increase the occurrence of muscle breakdown (rhabdomyolysis) which is seen when these drugs accumulate in the body.

Clarithromycin and ketoconazole may increase blood concentrations of Invirase and cause increased severity or frequency of side effects from Invirase.

Invirase also increases the concentration of clarithromycin.

Rifampin and rifabutin decrease blood concentrations of Invirase and may decrease the effectiveness of Invirase.

The combination of Invirase and ritonavir should not be combined with rifampin due to the risk of severe liver damage.

When digoxin is taken by patients receiving Invirase with ritonavir, the amount of digoxin in the body can increase, possibly leading to serious side effects.

Use of Invirase during pregnancy has not been adequately evaluated. It is unknown if Invirase passes into breast milk. HIV-infected mothers should not breastfeed because of the potential risk of transmitting HIV to an infant.

What are the important side effects of Invirase (saquinavir)?

Invirase can cause serious side effects such as

  • Diabetes and high blood sugar. Some people who take protease inhibitors including Invirase get new or more serious diabetes, or high blood sugar.
    • Tell your healthcare provider if you notice an increase in thirst or urinate more often than normal during treatment with Invirase.
  • Liver problems. People with liver problems such as Hepatitis B or C, cirrhosis or have a history of alcoholism may have worsening liver problems.
    • Tell your healthcare provider right away if you have any of these signs and symptoms of liver problems:
      • loss of appetite
      • yellowing of your skin or whites of your eyes (jaundice)
      • dark-colored urine
      • pale-colored stools (bowel movements)
      • itchy skin
      • stomach area (abdominal) pain
  • Increased bleeding in people with hemophilia. Some people with hemophilia have increased bleeding with protease inhibitors including Invirase.
  • Increase in certain fat (cholesterol and triglycerides) levels in your blood. Your healthcare provider will check your blood for high levels of cholesterol and triglycerides before you start Invirase and during treatment with Invirase.
    • Changes in body fat can happen in people who take HIV-1 medicine.
    • These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breasts, and around the middle of your body (trunk).
    • Loss of fat from the legs, arms and face may also happen. The exact cause and long-term health effects of these conditions are not known.
  • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time.
    • Tell your healthcare provider if you start having new or worse symptoms of infection after starting your HIV-1 medicine.

The most common side effects of Invirase include

These are not all of the possible side effects of Invirase. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Genentech at 1-888-835-2555.

Invirase (saquinavir) side effects list for healthcare professionals

The following adverse reactions are discussed in greater detail in other sections of the labeling:

  • PR Interval Prolongation
  • QT Interval Prolongation

Clinical Trial Experience In Adult Subjects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The original Invirase safety database consisted of a total of 574 adult subjects who received 600 mg of saquinavir mesylate capsules (hard gel) alone or in combination with zidovudine (ZDV) or zalcitabine (ddC).

Combination dosing with ritonavir is based on 352 HIV-1 infected subjects and 166 healthy subjects who received various combinations of either saquinavir mesylate capsules (hard gel or soft gel) with ritonavir.

The recommended dose of Invirase is 1,000 mg twice daily co-administered with ritonavir 100 mg twice daily. Table 1 lists Grade 2, 3 and 4 adverse events that occurred in ≥2% of subjects receiving saquinavir mesylate capsules (soft gel) with ritonavir (1000/100 mg bid).

Table 1 : Grade 2, 3 and 4 Adverse Events (All Causalitya) Reported in ≥2% of Adult Subjects in the MaxCmin 1 Study of Saquinavir Mesylate Capsules (soft gel) in Combination with Ritonavir 1000/100 mg Twice a Day

Adverse EventsSaquinavir Mesylate Capsules (soft gel) 1000 mg plus Ritonavir 100 mg bid (48 weeks)
N=148 n (%=n/N)
Endocrine Disorders
Diabetes mellitus/hyperglycemia4 (3)
Lipodystrophy8 (5)
Gastrointestinal Disorders
Nausea16 (11)
Vomiting11 (7)
Diarrhea12 (8)
Abdominal Pain9 (6)
Constipation3 (2)
General Disorders and Administration Site Conditions
Fatigue9 (6)
Fever5 (3)
Musculoskeletal Disorders
Back Pain3 (2)
Respiratory Disorders
Pneumonia8 (5)
Bronchitis4 (3)
Influenza4 (3)
Sinusitis4 (3)
Dermatological Disorders
Rash5 (3)
Pruritus5 (3)
Dry lips/skin3 (2)
Eczema3 (2)
a Includes events with unknown relationship to study drug

  • Limited experience is available from three trials investigating the pharmacokinetics of the Invirase 500-mg film-coated tablet compared to the 200-mg saquinavir mesylate capsules (hard gel) in healthy volunteers (n=140). In two of these trials, saquinavir was combined with ritonavir; in the other trial, saquinavir was administered as single drug.
  • The Invirase tablet and the saquinavir mesylate capsule (hard gel) were similarly tolerated.
  • The most common adverse events were gastrointestinal disorders (nausea, vomiting, and diarrhea).
  • Similar bioavailability was demonstrated and no clinically significant differences in saquinavir exposures were seen.
  • Thus, similar safety profiles are expected between the two Invirase formulations.

A study investigating the drug-drug interaction of rifampin 600 mg/day daily and Invirase 1000 mg/ritonavir 100 mg twice daily enrolled 28 healthy volunteers.

  • Eleven of 17 (65%) healthy volunteers exposed concomitantly to rifampin and Invirase/ritonavir developed severe hepatocellular toxicity which presented as increased hepatic transaminases.
  • In some subjects, transaminases increased up to > 20-fold the upper limit of normal and were associated with gastrointestinal symptoms, including abdominal pain, gastritis, nausea, and vomiting.
  • Following discontinuation of all three drugs, clinical symptoms abated and hepatic transaminases normalized.
Additional Adverse Reactions Reported During Clinical Trials With Saquinavir

Blood and lymphatic system disorders: anemia, hemolytic anemia, leukopenia, lymphadenopathy, neutropenia, pancytopenia, thrombocytopenia

Cardiac disorders: heart murmur, syncope

Ear and labyrinth disorders: tinnitus

Eye disorders: visual impairment

Gastrointestinal disorders: abdominal discomfort, ascites, dyspepsia, dysphagia, eructation, flatulence, gastritis, gastrointestinal hemorrhage, intestinal obstruction, mouth dry, mucosal ulceration, pancreatitis

General disorders and administration site conditions: anorexia, asthenia, chest pain, edema, lethargy, wasting syndrome, weight increased

Hepatobiliary disorders: chronic active hepatitis, hepatitis, hepatomegaly, hyperbilirubinemia, jaundice, portal hypertension

Immune system disorders: allergic reaction

Investigations: ALT increase, AST increase, blood creatine phosphokinase increased, increased alkaline phosphatase, GGT increase, raised amylase, raised LDH

Metabolism and nutrition disorders: increased or decreased appetite, dehydration, hypertriglyceridemia

Musculoskeletal and connective tissue disorders: arthralgia, muscle spasms, myalgia, polyarthritis

Neoplasms benign, malignant and unspecified (including cysts and polyps): acute myeloid leukemia, papillomatosis

Nervous system disorders: confusion, convulsions, coordination abnormal, dizziness, dysgeusia, headache, hypoesthesia, intracranial hemorrhage leading to death, loss of consciousness, paresthesia, peripheral neuropathy, somnolence, tremor

Psychiatric disorders: anxiety, depression, insomnia, libido disorder, psychotic disorder, sleep disorder, suicide attempt

Renal and urinary disorders: nephrolithiasis

Respiratory, thoracic and mediastinal disorders: cough, dyspnea

Skin and subcutaneous tissue disorders: acne, alopecia, dermatitis bullous, drug eruption, erythema, severe cutaneous reaction associated with increased liver function tests, Stevens-Johnson syndrome, sweating increased, urticaria

Vascular disorders: hypertension, hypotension, thrombophlebitis, peripheral vasoconstriction

Clinical Trial Experience In Pediatric Subjects

Limited safety data are available from two pediatric clinical trials of saquinavir mesylate capsules (hard gel) (approximately 50 mg per kg twice daily) used in combination with either low dose ritonavir or lopinavir/ritonavir.

These trials enrolled pediatric subjects aged 4 months to 16 years old. In the HIVNAT 017 study (saquinavir mesylate capsules (hard gel) + lopinavir/ritonavir), adverse events were reported in 90% of the 50 subjects enrolled.

The most commonly reported adverse events considered related to study treatment were diarrhea (18%) and vomiting (10%). In the NV20911 study (saquinavir mesylate capsules (hard gel) + ritonavir), 4 subjects (22% of 18 enrolled) experienced adverse events that were considered related to Invirase + ritonavir.

These events (n) were

All reported adverse events were mild or moderate in intensity. The adverse reaction profile of Invirase in the pediatric trials is similar to that observed in adult trials.

Postmarketing Experience

Additional adverse events identified during postmarketing use are similar to those observed in clinical trials with Invirase, saquinavir mesylate capsules (hard gel and soft gel) alone or in combination with ritonavir.

Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Invirase exposure. In addition, torsade de pointes has been reported rarely.

What drugs interact with Invirase (saquinavir)?

Drug interaction studies have been completed with Invirase and saquinavir mesylate capsules (hard gel and soft gel). Observations from drug interaction studies with saquinavir mesylate capsules (soft gel) may not be predictive for Invirase/ritonavir.

Because ritonavir is coadministered with Invirase, prescribers should also refer to the prescribing information for ritonavir regarding drug interactions associated with this agent.

Potential For Invirase/Ritonavir To Affect Other Drugs

The combination Invirase/ritonavir is a potent inhibitor of CYP3A and may significantly increase the exposure of drugs primarily metabolized by CYP3A.

Drugs that are contraindicated specifically due to the observed or expected magnitude of interaction and potential for serious or life-threatening adverse events are listed in Section 4 Contraindications. Coadministration with other CYP3A substrates may require a dose adjustment or additional monitoring (see Table 2).

Potential For Other Drugs To Affect Invirase/Ritonavir

The metabolism of saquinavir is mediated primarily by CYP3A. Additionally, saquinavir is a substrate for P-glycoprotein (P-gp).

Therefore, drugs that affect CYP3A and/or P-gp may modify the pharmacokinetics of saquinavir.

Coadministration with drugs that are potent inducers of CYP3A (e.g., phenobarbital, phenytoin, carbamazepine) may result in decreased plasma concentrations of saquinavir and reduced therapeutic effect.

Established And Other Potentially Significant Drug Interactions

Based on the finding of dose-dependent prolongations of QT and PR intervals in healthy volunteers receiving Invirase/ritonavir, additive effects on QT and/or PR interval prolongation may occur with certain members of the following drug classes:

  • antiarrhythmics class IA or class III,
  • neuroleptics,
  • antidepressants,
  • PDE5 inhibitors (when used for pulmonary arterial hypertension),
  • antimicrobials,
  • antihistaminics and
  • others.

This effect might lead to an increased risk of ventricular arrhythmias, notably torsade de pointes. Therefore, concurrent administration of these agents with Invirase/ritonavir is contraindicated.

Table 2 provides examples of established or potentially clinically significant drug interactions. This table includes potentially significant interactions but is not all inclusive. Alteration in dose or avoidance of the combination may be recommended depending on the interaction.

Table 2 : Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or on Predicted Interaction with Invirase/Ritonavir1

Concomitant Drug Class: Drug NameEffectc on Concentration of Saquinavir or Concomitant DrugClinical Comment
HIV-1 Antiviral Agents
Non-nucleoside reverse transcriptase inhibitor: Rilpivirine↑ RilpivirineCo-administration with Invirase/ritonavir and switching from rilpivirine to Invirase/ritonavir within 2 weeks is contraindicated due to the potential for life-threatening cardiac arrhythmia.
Non-nucleoside reverse transcriptase inhibitor: Delavirdineb↑Saquinavir Effect on delavirdine is not well establishedAppropriate doses of the combination with respect to safety and efficacy have not been established. Co-administration is not recommended.
Liver function should be monitored frequently if this combination is prescribed.
Efavirenza, nevirapineb↓Saquinavir ↔ EfavirenzAppropriate doses of the combination of efavirenz or nevirapine and Invirase/ritonavir with respect to safety and efficacy have not been established. Co-administration is not recommended.
HIV-1 protease inhibitor: Atazanavir↑Saquinavir
↑Ritonavir
↑Atazanavir
Co-administration is contraindicated with Invirase/ritonavir due to the potential for serious and/or life-threatening cardiac arrhythmia.
HIV-1 protease inhibitor: Indinavirb↑ Saquinavir
↑ Indinavir
Appropriate doses of the combination of indinavir and Invirase/ritonavir with respect to safety and efficacy have not been established. Co-administration is not recommended. Increased concentrations of indinavir may result in nephrolithiasis. For further details see complete prescribing information for indinavir.
Lopinavir/ritonavira (coformulated tablet)↔ Saquinavir ↔ Lopinavir ↓ RitonavirEvidence from several clinical trials indicates that saquinavir concentrations achieved with the saquinavir and lopinavir/ritonavir combination are similar to those achieved following Invirase/ritonavir 1000/100 mg. The recommended dose for this combination is Invirase 1000 mg plus lopinavir/ritonavir 400/100 mg bid.
Lopinavir/ritonavir in combination with Invirase should be used with caution. Additive effects on QT and/or PR interval prolongation may occur with Invirase.
Nelfinavira↑SaquinavirCombining saquinavir/ritonavir with nelfinavir is not recommended
Tipranavir/ritonavira↓ SaquinavirCombining saquinavir with tipranavir/ritonavir is not recommended.
HIV-1 CCR5 antagonist: Maraviroc↑MaravirocMaraviroc dose should be 150 mg twice daily when co-administered with Invirase/ritonavir. For further details see complete prescribing information for Selzentry® (maraviroc).
Other Agents
Alpha 1-adrenoreceptor antagonist: Alfuzosin↑ AlfuzosinCo-administration is contraindicated with Invirase/ritonavir as potentially increased alfuzosin concentrations can result in hypotension, and potentially life-threatening cardiac arrhythmia.
Antiarrhythmics: Amiodarone, bepridil, dofetilide, flecainide, lidocaine (systemic), propafenone, quinidine↑Amiodarone
↑ Bepridil
↑Dofetilide
↑ Flecainide
↑ Lidocaine (systemic)
↑Propafenone
↑Quinidine
Co-administration is contraindicated with Invirase/ritonavir due to the potential for serious and/or life-threatening cardiac arrhythmia.
Antiarrhythmics: Ibutilideb SotalolbEffects on ibutilide, sotalol, and saquinavir concentrations are not well-establishedAdditive effects on QT and/or PR interval prolongation may occur with Invirase/ritonavir. Co-administration of Invirase/ritonavir and ibutilide or sotalol is not recommended.
Anticoagulant: Warfarinb↑ WarfarinConcentrations of warfarin may be affected. It is recommended that INR (international normalized ratio) be monitored.
Anticonvulsants: Carbamazepineb, phenobarbitalb, phenytoinb↓ Saquinavir
Effect on carbamazepine, phenobarbital, and phenytoin is not well established
Saquinavir may be less effective due to decreased saquinavir plasma concentrations in patients taking these agents concomitantly. Coadministration is not recommended.
Antidepressant: Trazodone↑ TrazodoneCo-administration is contraindicated with Invirase/ritonavir as increased trazodone concentrations can result in potentially life-threatening cardiac arrhythmia.
Tricyclic antidepressantsb Amitriptyline, clomipramine, imipramine, maprotiline↑ TricyclicsTherapeutic concentration monitoring is recommended for tricyclic antidepressants when co-administered with Invirase/ritonavir.
Other antidepressants: Nefazodoneb↑ SaquinavirUse with caution due to possible cardiac arrhythmias. Clinical monitoring for saquinavir toxicity is recommended.
Antifungals: Ketoconazolea,↔Saquinavir
↔ Ritonavir
↑Ketoconazole
When Invirase/ritonavir and ketoconazole are co-administered, plasma concentrations of ketoconazole are increased (see Table 5). Hence, doses of ketoconazole or itraconazole > 200 mg/day are not recommended.
Itraconazoleb↑ Itraconazole
↑Saquinavir
Clinical monitoring for saquinavir toxicity is recommended. Use with caution due to possible cardiac arrhythmias.
Anti-gout: Colchicine↑ColchicineTreatment of sout flares-co-administration of colchicine in patients on Invirase/ritonavir: 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days.
Treatment of familial Mediterranean fever (FMF) co-administration of colchicine in patients on Invirase/ritonavir:
Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).
Prophylaxis of eout flares-co-administration of colchicine in patients on Invirase/ritonavir:
If the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day.
If the original colchicine regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.
Patients with renal or hepatic impairment should not be given colchicine with Invirase/ritonavir.
Anti-infectives: Clarithromycin, Erythromycin
Halofantrine
Pentamidine
↑ Clarithromycin↑ Erythromycin ↑Halofantrine
↔ Pentamidine
Co-administration is contraindicated with Invirase/ritonavir due to the potential for serious and/or life-threatening cardiac arrhythmia.
Anti-infectives: Streptogramin antibiotics (quinupristin/dalfopristinb) Fusidic AcidStreptogramin antibiotics such as quinupristin/ dalfopristin inhibit CYP3A4; saquinavir concentrations may be increased
↑ Saquinavir
↑ Fusidic Acid
↑ Ritonavir
Monitoring for saquinavir toxicity is recommended. Use with caution due to possible cardiac arrhythmias.
Concomitant use of fusidic acid and Invirase/ritonavir is not recommended due to potential for increased mutual toxicities. The interaction between Invirase/ritonavir and fusidic acid has not been formally evaluated. Co-administration of fusidic acid and Invirase/ritonavir can cause increased plasma concentrations of fusidic acid, saquinavir and ritonavir.
Antimycobacterial: Rifabutina Dapsoneb↔ Saquinavir
↑ Rifabutin
↔ Ritonavir
↑ Dapsone
No dose adjustment of Invirase/ritonavir (1000/100 mg bid) is required if Invirase/ritonavir is administered in combination with rifabutin.
Dosage reduction of rifabutin by at least 75% of the usual dose of 300 mg/day is recommended (i.e., a maximum dose of 150 mg every other day or three times per week). Increased monitoring for adverse events including neutropenia and liver enzyme levels is warranted in patients receiving the combination.
Consider monitoring rifabutin concentrations to ensure adequate exposure.
Co-administration of saquinavir/ritonavir with drugs that are metabolized by CYP3A4 pathway may result in elevated plasma concentrations of these drugs. Co-administration with oral dapsone is not recommended.
Antimycobacterial: Rifampin↑ RifampinCo-administration is contraindicated with Invirase/ritonavir as part of an ART regimen due to the risk of severe hepatocellular toxicity.
Antipsychotic: Quetiapine↑ QuetiapineInitiation of Invirase with ritonavir in patients taking auetiapine:
Consider alternative antiretroviral therapy to avoid increases in quetiapine drug exposures. If co-administration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring.
Initiation of quetiapine in patients takins Invirase with ritonavir:
Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine.
Antipsychotic: Lurasidone↑ LurasidoneCo-administration is contraindicated with Invirase/ritonavir due to the potential for serious and/or life-threatening reactions.
Antipsychotics: clozapine, haloperidol, pimozide, sertindole, ziprasidone, phenothiazines (e.g. chlorpromazine, mesoridazine, thioridazine).↑Clozapine ↑Haloperidol
↑ Pimozide
↑Ziprasidone
↑ Chlorpromazine
↑ Mesoridazine
↑ Sertindole
↑ Thioridazine
Co-administration is contraindicated with Invirase/ritonavir due to the potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Benzodiazepine: Triazolam, orally administered Midazolam↑Midazolam
↑ Triazolam
Co-administration is contraindicated with Invirase/ritonavir due to the potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression.
Benzodiazepinesb: Alprazolam, clorazepate, diazepam, flurazepam↑ BenzodiazepinesClinical significance is unknown. Careful monitoring of patients for benzodiazepine effects is warranted; a decrease in benzodiazepine dose may be needed.
Intravenously administered Midazolam↑ MidazolamIf Invirase/ritonavir is co-administered with parenteral midazolam, close clinical monitoring for respiratory depression and/or prolonged sedation should be exercised and dosage adjustment should be considered.
Calcium channel blockersb: Diltiazem, felodipine, nifedipine, nicardipine, nimodipine, verapamil, amlodipine, nisoldipine, isradipine↑Calcium channel blockersClose clinical monitoring of patients is recommended.
Systemic/Inhaled/Nasal/ Ophthalmic Corticosteroids: e.g. betamethasone, budesonide, ciclesonide, dexamethasoneb, fluticasoneb, methylprednisolone, mometasone, prednisone, triamcinolone↓ SaquinavirCo-administration of Invirase/ritonavir with systemic dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to saquinavir. Consider alternative corticosteroids.
↑CorticosteroidsCo-administration of Invirase/ritonavir with corticosteroids of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone and prednisolone (for which PK and/or PD are less affected by strong CYP3A inhibitors relative to other steroids) should be considered, particularly for long term use.
Digitalis Glycosides: Digoxina↑Digoxin
Increases in serum digoxin concentration were greater in female subjects as compared to male subjects when digoxin was coadministered with Invirase/ritonavir.
Caution should be exercised when Invirase/ritonavir and digoxin are co-administered; serum digoxin concentrations should be monitored and the dose of digoxin may need to be reduced when coadministered with Invirase/ritonavir.
Endothelin receptor antagonists: Bosentan↑BosentanCo-administration of bosentan in patients on Invirase/ritonavir:
In patients who have been receiving Invirase/ritonavir for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability.
Co-administration of Invirase/ritonavir in patients on bosentan:
Discontinue use of bosentan at least 36 hours prior to initiation of Invirase/ritonavir.
After at least 10 days following the initiation of Invirase/ritonavir, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability.
Ergot derivatives: Dihydroergotamine, ergonovine, ergotamine, methylergonovine↑ Dihydroergotamine,
↑Ergonovine,
↑Ergotamine,
↑ Methylergonovine
Co-administration is contraindicated in Invirase/ritonavir due to the potential for serious and life-threatening reactions such as ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues.
Herbal Product: St. John’s wortb (hypericum perforatum)
Garlic Capsulesb
↓ SaquinavirHerbal products containing St. John’s wort should not be used concomitantly with Invirase/ritonavir because co-administration may lead to loss of virologic response and possible resistance to Invirase or to the class of protease inhibitors.
Co-administration of garlic capsules and saquinavir is not recommended due to the potential for garlic capsules to induce the metabolism of saquinavir which may result in sub-therapeutic saquinavir concentrations.
HMG-CoA reductase inhibitors: Lovastatin, Simvastatin↑Lovastatin
↑Simvastatin
Co-administration is contraindicated with Invirase/ritonavir due to the potential for myopathy including rhabdomyolysis.
HMG-CoA reductase inhibitorsb: Atorvastatin↑AtorvastatinTitrate atorvastatin dose carefully and use the lowest dose necessary; do not exceed atorvastatin 20 mg/day. Patients should be carefully monitored for signs and symptoms of myopathy (e.g., muscle weakness, muscle pain, rising creatine kinase).
Immunosuppressants: Tacrolimus↑TacrolimusCo-administration is contraindicated with Invirase/ritonavir due to the potential for serious and/or life-threatening cardiac arrhythmia.
Immunosuppressants: Cyclosporineb, rapamycinb↑ImmunosuppressantsTherapeutic concentration monitoring is recommended for immunosuppressant agents when co-administered with Invirase/ritonavir.
Inhaled beta agonist: Salmeterol↑SalmeterolConcurrent administration of salmeterol with Invirase/ritonavir is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia.
Narcotic analgesic: Methadonea↓ MethadoneDosage of methadone may need to be increased when coadministered with Invirase/ritonavir. Use with caution. Additive effects on QT and/or PR interval prolongation may occur with Invirase/ritonavir.
Oral contraceptives: Ethinyl estradiolb↓ Ethinyl estradiolAlternative or additional contraceptive measures should be used when estrogen-based oral contraceptives and Invirase/ritonavir are co-administered.
PDE5 inhibitors (phosphodiesterase type 5 inhibitors): Sildenafila, vardenafilb, tadalafilb↑Sildenafil
↔Saquinavir
↑ Vardenafil
↑ Tadalafil
Only the combination of sildenafil with saquinavir mesylate capsules (soft gel) has been studied at doses used for treatment of erectile dysfunction.
May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, syncope, visual disturbances, and priapism.
Use of PDE-5 inhibitors for pulmonary arterial hypertension (PAH):
  • Co-administration is contraindicated with Invirase/ritonavir when sildenafil (Revatio) is used for the treatment of pulmonary arterial hypertension (PAH).

The following dose adjustments are recommended for use of tadalafil (Adcirca) with Invirase/ritonavir:
Co-administration of Adcirca in patients on Invirase/ritonavir:
In patients receiving Invirase/ritonavir for at least one week, start Adcirca at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
Co-administration of Invirase/ritonavir in patients on Adcirca:
Avoid use of Adcirca during the initiation of Invirase/ritonavir. Stop Adcirca at least 24 hours prior to starting Invirase/ritonavir. After at least one week following the initiation of Invirase/ritonavir, resume Adcirca at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
Use of PDE5 inhibitors for erectile dysfunction:
Use sildenafil with caution at reduced doses of 25 mg every 48 hours with increased monitoring of adverse events when administered concomitantly with Invirase/ritonavir.
Use vardenafil with caution at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring of adverse events when administered concomitantly with Invirase/ritonavir.
Use tadalafil with caution at reduced doses of no more than 10 mg every 72 hours with increased monitoring of adverse events when administered concomitantly with Invirase/ritonavir.

Proton pump inhibitors: Omeprazolea↑ SaquinavirWhen Invirase/ritonavir is co-administered with omeprazole, saquinavir concentrations are increased significantly. If omeprazole or another proton pump inhibitor is taken concomitantly with Invirase/ritonavir, caution is advised and monitoring for potential saquinavir toxicities is recommended, particularly gastrointestinal symptoms, increased triglycerides, deep vein thrombosis, and QT prolongation. Use with caution due to possible cardiac arrhythmias.
Tyrosine kinase inhibitors:
Dasatinib
Sunitinib
↑ Dasatinib
↑ Sunitinib
Co-administration is contraindicated with Invirase/ritonavir due to potentially life-threatening cardiac arrhythmia.
Vasodilators (peripheral): Intravenously administered↑VincamineMonitoring for vincamine toxicity is recommended. Use with caution due to potential cardiac arrhythmias.
Vincamine
Other drugs that are substrates of CYP3A: Disopyramide
Quinine
↑ Disopyramide
↑ Quinine
Co-administration is contraindicated with Invirase/ritonavir due to the potential for serious and/or life-threatening cardiac arrhythmia.
Other drugs that are substrates of CYP3A: Fentanylb
Alfentanilb
↑ Fentanyl
↑ Alfentanil
Co-administration with these drugs may accentuate the side effects reported with use of fentanyl or alfentanil including respiratory depression, apnea and bradycardia.
1 This list provides examples of established or potentially clinically significant drug interactions drugs with Invirase/ritonavir and may not be exhaustive
aSee Table 5 and Table 6 for magnitude of interactions.
bInvirase/ritonavir interaction has not been evaluated.
cObserved or predicted effect.

Drugs Without Clinically Significant Interactions With Invirase/Ritonavir

Based on drug interaction studies conducted with Invirase/ritonavir, no clinically significant effect was observed for saquinavir when coadministered with fosamprenavir.

No clinically significant effect was observed for enfuvirtide when coadministered with Invirase/ritonavir.

Summary

Invirase (saquinavir) is a type of antiviral medication called a protease inhibitor used to treat infections with the human immunodeficiency virus (HIV). Common side effects of Invirase include diarrhea, nausea, vomiting, stomach pain, tiredness, and changes in the shape or location of body fat (especially in the arms, legs, face, neck, breasts, and waist). The combination of Invirase and ritonavir should not be combined with rifampin due to the risk of severe liver damage. Use of Invirase during pregnancy has not been adequately evaluated. It is unknown if Invirase passes into breast milk.

Treatment & Diagnosis

Medications & Supplements

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Medically Reviewed on 6/19/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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